Hematopiesis involves proliferation of hematopoietic stem cells (HSCs) and their differentiation into progenitors (e.g., erythroprogenitor cells). HSCs give rise to mature cells of all lineages of blood and immune systems.
Over the course of several decades, multiple lineage specific transcriptional factors, such as GATA-1 and EKLF, have been shown to play critical roles in hematopoiesis/erythropoiesis. Yet, the cell-intrinsic factors that allow expansion of hematopoiesis and erythropoiesis remain not completely understood. It has been shown that over-expression of several cell-intrinsic factors, such as WNT3a, beta-catenin, and HOXB4, leads to significant expansion of HSCs in mice. However, their effects on expansion of human HSCs are limited.
The difficulty in expanding human HSCs ex vivo represents a major challenge in human HSC-based therapeutic applications, e.g., reconstitution of the hematopoietic system. There is a need to develop a method of effectively expanding human HSCs.